VASCULARIZATION OF TUMORS
VASCULARIZATION OF TUMORS
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DOI：
10.1038/scientificamerican0576-58
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发表时间：
1976-01-01
影响因子：
3
通讯作者：
FOLKMAN, J
中科院分区：
文献类型：
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作者：
FOLKMAN, J
在每个人的身体里，无数的正常细胞日夜忙碌地繁殖着。一个成年人每秒至少有400万个细胞分裂;一天分裂3500亿个;一年分裂1014个以上。当一个正常的细胞经过一个分裂周期，它有可能成为恶性的。然而，大多数人一生中不会患上致命的癌症。很明显，机体必须具有显著的控制系统，以防止异常细胞产生或发展为晚期恶性肿瘤。癌症统计数据给人的印象是，几乎没有控制系统在起作用。在美国，每年大约有60万例新的癌症病例被诊断出来，或者每天大约有1,600例。更深入的分析提供了不同的视角。在每个癌症患者中，肿瘤可能来自单个异常细胞。由于这个国家的215万人每天产生大约1020个正常细胞，因此给定细胞是能够引发肿瘤的异常细胞的概率非常小，大约为1017分之一。这种非同寻常的”质量控制”是如何实现的？为什么会失败？一个孤立的恶性细胞是如何生存的？这样一个幸存者必须获得什么样的特征才能最终成为一个”成功的”肿瘤？我们的知识是贫乏的。在分子水平上有一些关于控制点的信息。例如，存在检查分裂细胞的DNA并修复转录中的断裂、缺失和错误的监测系统。在单个细胞和细胞群水平上也有一些信息。在这里，我想讨论实体瘤发展的关键时期。多年来，我和我的同事一直在研究犹大·福克曼（Judah Folkman）的一个恶性细胞小菌落牢固建立之后，但在它获得快速增殖和侵入能力之前的时期。在人类中，原位病变通常是可以检测到实体瘤的最早阶段。这种病变通常直径只有几毫米，呈半扁平状。如果它存在于皮肤，膀胱或子宫颈中，它可以被看到和识别。目前还不能诊断出身体其他器官中的类似肿瘤。在这个无害的阶段，肿瘤仍然是无血管的，也就是说，它缺乏自己的血管网络来提供营养，包括氧气和排出废物。因为营养物和废物的转移必须通过周围健康组织的扩散来完成，所以原位病变不能生长超过一定的体积。达到一个稳定状态，其中新生成的细胞与垂死的细胞平衡。在一个近似球形的群体中，稳定状态下的直径通常是几毫米或更小，除非殖民地完全变成薄片，否则生长就会停止。即使是潜在的最恶性的肿瘤也可能在这个“多瘤”阶段徘徊多年。由于这种早期微小肿瘤内的细胞似乎彼此粘附得很强，它们通常不会侵入、游走或以其他方式破坏宿主的完整性。
In every human being myriads of normal cells are busily reproducing day and night. In an adult at least four million cells divide every second; 350 billion divide in a day; more than 1014 divide in a year. When a normal cell passes through a cycle of division, it has the potential of becoming malignant. Nevertheless, the majority of people go through life without developing a fatal cancer. Clearly the body must possess remarkable control systems for prevent ing aberrant cells from arising or from pro gressing to a terminal malignancy. The cancer statistics give the impression that few if any control systems are at work. In the US about 600,000 new cases of can cer are diagnosed every year, or approxi mately 1,600 every day. Closer analysis pro vides a different perspective. In each person with cancer the tumor probably arises from a single aberrant cell. Since the 2 15 million people in this country generate about 1020 normal cells every day, the probability that a given cell will be a deviant one capable of initiating a tumor is exceedingly small, on the order of one in 1017. How is this extraordinary" quality con trol" accomplished? Why does it fail? How does a lone malignant cell survive? What characteristics must such a survivor acquire to ultimately become a" successful" tumor? Our knowledge is meager. There is some information about control points at the mo lecular level. For example, there are moni toring systems that inspect the DNA of di viding cells and repair breaks, deletions and errors in transcription. There is also some information at the level of individual cells and cell populations. Here I should like to discuss a critical period in the development of solid tumors. For a number of years my colleagues and I have been studying the pe riod after a tiny colony of malignant cells by Judah Folkman has become firmly established but before it has acquired the capacity for rapid prolifer ation and invasiveness. In human beings the in situ lesion is often the earliest stage at which a solid tumor can be detected. Such a lesion is usually only a few millimeters in diameter and semiflattened. If it is present in the skin, the bladder or the cervix, it can be seen and recognized. Similar tumors in other organs of the body cannot be diag nosed at present.At this harmless stage the'tumor is still avascular, that is, it lacks its own network of blood vessels for supplying nutrients, in cluding oxygen, and for removing wastes. Because the transfer of nutrients and wastes has to be accomplished by diffusion through the surrounding healthy tissue the in situ lesion cannot grow beyond a certain vol ume. A steady state is reached in which newly generated cells are balanced by dying cells. In a population that is roughly sphe roidal the steady-state diameter is usually a few millimeters or less. Unless the colony flattens completely into a thin sheet, growth stops. Even tumors that are potentially the most malignant may linger in this" dor mant" stage for years. Since cells within such early microtumors seem to adhere strongly to one another, they usually do not invade, wander through or otherwise vio late the integrity of their host.